Table 1.
Cerebrovascular function in migraineurs compared to controls during the migraine free period.
| Study | Population and numbers | Area of assessment | Assessment | Key findings | NOS |
|---|---|---|---|---|---|
| TCD Studies | |||||
| Altamura et al.51 | Total = 129MA = 56 (46 F/10M) Stroke = 20 (9 F/11M) Controls = 53 (42 F/11M) | Unilateral MCA (left) Unilateral PCA (right) | CVR to BHT(30s breath hold) | MA had a higher BHI compared to controls (and stroke patients). | 8 |
| Lee et al.56 | Total = 353MX = 248 (201 F/47M) Controls = 105 (86 F/19M) | BABilateral MCA Bilateral PCA | CVR to BHT (30 s breath hold) | MX had a lower BHI compared to controls. | 8 |
| Altamura et al.87 | Total = 70MA = 39 (34 F/5M) Stroke = 15 (8 F/7M) Controls = 16 (8 F/8M) | Unilateral MCA (left) Unilateral PCA (right) | CVR to BHT (30s breath hold) | MA had a higher BHI compared to controls (and stroke patients). | 5 |
| Gollion et al.52 | Total = 44MA = 22 (18 F/4M) Controls = 22 (17 F/5M) | Unilateral MCA (right) | CVR to BHT (30s breath hold) | No difference. | 8 |
| Cerebral autoregulation (Dx, Mx, phase, gain) | No difference. | ||||
| Karacay Ozkalayci et al.17 | Total = 75MA = 10 (MD) MO = 30 (MD) TTH = 10 (MD) Controls = 25 (17 F/8M) | Bilateral ACA BABilateral MCA Bilateral PCA Bilateral VA Bilateral MCA | Resting MBFV | No difference. | 7 |
| Podgorac et al.16 | Total = 273MA = 100 (71 F/29M) MO = 70 (61 F/9M) TTH = 38 (21 F/17M) CH = 35 (10 F/25M) Controls = 30 (13 F/17M) | CVR to BHT(30s breath hold) | MA had a higher BHI compared to controls. | 8 | |
| Resting MBFV | No difference. | ||||
| Choi et al.18 | Total = 84EM = 28 (24 F/4M) RCVS = 28 (24 F/4M) Controls = 28 (25 F/3M) | BABilateral MCABilateral PCA | CVR to BHT (30 s breath hold) | MD. | 8 |
| Resting MBFV | MD. | ||||
| Gonzalez-Quintanilla et al.53 | Total = 113CM = 35 (31 F/4M) EM = 37 (27 F/10M) Controls = 41 (29 F/12M) | BABilateral MCA | CVR to BHT(breath hold time not specified) | CM and EM had a lower BHI compared to controls. | 7 |
| Akgun et al.19 | Total = 60CM = 31 (MD) Controls = 29 (MD) | Bilateral MCA Bilateral PCA | CVR to BHT (30s breath hold) | CM had a lower BHI compared to controls. | 6 |
| Resting MBFV | No difference. | ||||
| Fabjan et al.20 | Total = 52MX = 29 (21 F/8M) Controls = 23 (13 F/10M) | Unilateral MCA (left) Unilateral PCA (right) | Neurovascular coupling (photic stimulation) | MD. | 7 |
| Resting MBFV | No difference. | ||||
| Rajan et al.12 | Total = 89MX = 45 (36 F/9M) Controls = 44 (31 F/13M) | BABilateral MCA Bilateral PCA | CVR to BHT (30s breath hold) | MX had a lower BHI in BA, left PCA and right PCA compared to controls. | 7 |
| Resting MBFV | No difference. | ||||
| Karadas et al.21 | Total = 40MA = 20 (15 F/5M) Controls = 20 (16 F/4M) | Bilateral MCABilateral PCA | CVR to BHT (100s breath hold) | MA had a higher BHI in the MCA and PCA compared to controls. | 8 |
| Resting MBFV | MA had a higher MBFV in the MCA and PCA compared to controls. | ||||
| Quirico et al.22 | Total = 30MO = 16 (MD) Controls = 14 (MD) | Unilateral MCA (right) | Resting MBFV | No difference. | N/A |
| Reinhard et al.23 | Total = 69MA = 17 (12 F/5M) MO = 17 (13 F/4M) Controls = 35 (26 F/9M) | Unilateral MCA (left) Unilateral PCA (right) | Resting MBFV, PI | No difference. | 7 |
| Cerebral autoregulation (phase, gain, Dx) | MA had higher Dx than controls in the MCA. | ||||
| Min et al.25 | Total = 36MA = 22 (14 F/8M) Controls = 14 (9 F/5M) | Bilateral PCA | Neurovascular coupling (20 s photic stimulus, then 20 s rest for 10 cycles) | No difference. | 6 |
| Resting MBFV | No difference. | ||||
| Perko et al.24 | Total = 60MA = 20 (16 F/4M)MO = 20 (16 F/4M) Controls = 20 (16 F/4M) | Unilateral MCA (right) Unilateral PCA (left) | CVR to L-arginine infusion (assessed 30 min after infusion) | MX had a lower CVR in the PCA. | 8 |
| Resting MBFV | No difference. | ||||
| Sousa et al.58 | Total = 284MX = 228 (189 F/39) Controls = 56 (31 F/25M) | Bilateral MCA | CVR to BHT(30s breath hold) | MX had a higher BHI compared to controls. | N/A |
| Wallasch et al.70 | Total = 120MX = 60 (50 F/10M) Controls = 60 (MD) | Bilateral MCA | Cerebral autoregulation (CVR to the Valsalva manoeuvre) | MX had a higher CVR to the Valsalva manoeuvre compared to controls. | N/A |
| El-Khawas et al.26 | Total = 41MX = 27 (23 F/4M) Controls = 14 (9 F/5M) | Bilateral MCA Bilateral PCA | CVR to hyperventilation (3-min hyperventilation) | MX had a lower CRI. | 9 |
| Resting MBFV | No difference. | ||||
| Wolf et al.67 | Total = 110MA = 70 (70 F/0M) Controls = 40 (30 F/10M) | Bilateral PCA | Neurovascular coupling (photic stimulation) | MX had a higher VEFR ((MBFV during stimulation – MBFV at rest)/MBFV at rest×100) compared to controls. | 8 |
| Zaletel et al.68 | Total = 70MA = 14 (MD) MO = 16 (MD) Controls = 40 (21 F/19M) | Unilateral MCA (left) Unilateral PCA (right) | Neurovascular coupling (photic stimulation) | MA and MO had a higher VEFR compared to controls. | N/A |
| Arjona et al.28 | Total = 131MO = 36 (26 F/10M) TTH = 51 (32 F/19M) Controls = 44 (25 F/19M) | Bilateral MCA | Resting MBFV, PI | No difference. | 8 |
| CVR to BHT (15-45 s breath hold) | No difference. | ||||
| Reinhard et al.27 | Total = 94MX = 19 (14 F/5M) Controls = 75 (33 F/42M) | Bilateral MCA | Resting MBFV | No difference. | 7 |
| Cerebral autoregulation (Dx, Mx, phase, gain) | No difference. | ||||
| MüLler and Marziniak69 | Total N = 55MX = 22 (19 F/3M) Controls = 33 (15 F/18M) | Bilateral MCA | Cerebral autoregulation (gain) | MX had a lower gain compared to controls. | N/A |
| Zaletel et al.47 | Total = 60MX = 30 (20 F/10M) Controls = 30 (22 F/8M) | Unilateral MCA (left) Unilateral PCA (right) | Neurovascular coupling (70 s photic stimulation stimulus, 30 s rest) | MX had a higher VEFR compared to controls. | N/A |
| Resting MBFV | No difference. | ||||
| Backer et al.64 | Total = 20 MX = 10 (MD) Controls = 10 (MD) | Unilateral MCA (left) Unilateral PCA (right) | Neurovascular coupling (photic stimulation) | MX had an exaggerated increase in CBFV at the beginning of the photic stimulation and a delayed decrease to baseline following photic stimulation compared to controls. | N/A |
| Nedeltchev et al.29 | Total = 38 MA = 19 (10 F/9M) Controls = 19 (8 F/11M) | Unilateral MCA (right) Unilateral PCA (left) | Neurovascular coupling (photic stimulation) (10 s stimulus, then 10 s rest for 10 cycles) | MA had a higher MBFV during photic stimulation compared to controls. | 7 |
| Resting MBFV | No difference. | ||||
| Silvestrini et al.57 | Total = 45MA = 15 (15 F/0M) MO = 15 (15 F/0M) Controls = 15 (15 F/0M) | BAUnilateral MCA (left or right side chosen at random) | CVR to BHT (30s breath hold) | MA had a lower BHI in BA compared to controls (and MO). | 8 |
| Dora et al.30 | Total = 31MO = 20 (18 F/2M) Controls = 11 (9 F/2M) | Bilateral MCA | CVR to BHT (30 s breath hold) | MO had a higher BHI compared to controls. | 8 |
| Resting MBFV, PI | No difference. | ||||
| Thomaides et al.31 | Total = 60MA = 45 (36 F/9M) Controls = 15 (12 F/3M) | Bilateral MCA | Resting MBFV | No difference. | 7 |
| Dora et al.32 | Total = 33MO = 23 (22 F/1M) Controls = 10 (9 F/1M) | Bilateral MCA | CVR to BHT (30s breath hold) | MO had a higher BHI compared to controls. | N/A |
| Resting MBFV, PI | No difference. | ||||
| Backer et al.65 | Total = 38MX= 19 (MD) Controls = 19 (MD) | Unilateral MCA (left) Unilateral PCA (right) | Neurovascular coupling (3 rounds of 57 s photic stimulation, 57 s rest) | MX had a higher initial increase of CBFV following the onset than controls in MCA and PCA. | N/A |
| Chernyshev et al.33 | Total = 69RSM = 25 (23 F/2M) LSM = 25 (23 F/2M) Controls =19 (9 F/10M) | BA Bilateral MCA | Resting MBFV, PI | RSM had higher MBFV in the BA and higher PI in the right MCA compared to LSM and controls. | 9 |
| Fiermonte et al.34 | Total = 42MA = 9 (4 F/5M) MO = 12 (8 F/4M) Controls = 21 (MD) | Bilateral MCA | CVR to BHT (breath hold time not specified) and hyperventilation (3-min hyperventilation) | MA had a higher CRI to hyperventilation compared to controls. | 6 |
| Resting MBFV | MA and MO had higher MBFV compared to controls. | ||||
| Heckmann et al.36 | Total = 45MA = 15 (11 F/4M) MO = 15 (11 F/4M) Controls = 15 (8 F/7M) | MCA (unclear if unilateral or bilateral) | Cerebral autoregulation (CVR to physical stress) | MA and MO had a lower ΔRI to physical stress compared to controls. | 7 |
| Resting MBFV, RI | No difference. | ||||
| Kastrup Aet al.35 | Total = 50MX = 20 (16 F/4M) Controls = 30 (17 F/13M) | Bilateral ACA Bilateral MCABilateral PCA | CVR to inhalation of 5%CO2 (duration not stated) | MX had higher CRI in the left ACA, right MCA and right PCA. | 8 |
| Resting MBFV | MX had higher MBFV in the right ACA and MCA compared to controls. | ||||
| Kastrup A et al.55 | Total = 40MX = 20 (17 F/3M) Controls = 20 (MD) | Bilateral MCA | CVR to inhalation of 5%CO2 (before metoprolol treatment initiated) | No difference. | N/A |
| Totaro et al.37 | Total = 90 MA = 30 (26 F/4M) MO = 30 (28 F/2M) Controls = 30 (27 F/3M) | Bilateral MCA (unclear if unilateral or bilateral) | CVR to inhalation of 5%CO2 (1–2 min inhalation), and hyperventilation (duration not stated) | MO had a lower CRI to CO2 inhalation compared to controls. | 7 |
| Resting MBFV | No difference. | ||||
| Silvestrini et al.38 | Total = 45MA = 15 (11 F/4M) MO = 15 (13 F/2M) Controls = 15 (MD) | Bilateral MCA | CVR to BHT (30s breath hold) | No difference. | 8 |
| Resting MBFV | No difference. | ||||
| Valikovics et al.60 | Total = 31MX = 12 (MD) Controls = 19 (MD) | Bilateral MCA | CVR to acetazolamide infusion | No difference | 7 |
| Fiermonteet al.40 | Total = 45MA = 15 (9 F/6M) MO = 15 (10 F/5M) Controls = 15 (8 F/7M) | Bilateral MCA | CVR to hyperventilation (3-min hyperventilation) | MA had a higher CRI than controls. | 7 |
| Resting MBFV, PI | MA and MO had lower PI than controls. | ||||
| Piccini et al.39 | Total = 27MO = 10 (7 F/3M) TTH = 10 (8 F/2M) Controls = 7 (5 F/2M) | MCA (unclear if unilateral or bilateral) | Resting MBFV, PI | No difference. | 7 |
| Thomsen et al.62 | Total = 50MA = 8 (MD) MO = 12 (MD) Controls = 30 (25F/5M) | Bilateral MCA | CVR to hyperventilation (90 s hyperventilation) | MA had a higher CRI, whereas MO had lower CRI compared to controls difference. | 7 |
| Abernathy et al.41 | Total = 220MX = 182 (141 F/41M) Controls = 38 (29 F/9M) | BABilateral ACABilateral ICABilateral MCABilateral PCABilateral VA | Resting MBFV | MX had higher MBFV compared to controls. | 8 |
| Anzola et al.43 | Total = 60MX = 30 (22 F/8M) Controls = 30 (18 F/12M) | Bilateral MCA | Resting MBFV | No difference. | 5 |
| CVR to hyperventilation (1-min hyperventilation) and the BHT (30 s breath hold) | MX had higher CVR to hyperventilation and lower CVR to hypercapnia compared to controls. | ||||
| Rieke et al.44 | Total = 50MX = 30 (24 F/6M) Controls = 20 (15 F/5M) | Unilateral MCA (ipsilateral to migraine) | CVR to inhalation of CO2 (% of CO2 not stated) | MX had lower CVR compared to controls. | N/A |
| Resting MBFV, PI | MX had higher resting MBFV compared to controls. | ||||
| Thomsen et al.42 | Total = 43MO = 17 (16 F/1M) TTH = 9 (8 F/1M) Controls = 17 (16 F/1M) | MCA(unclear if unilateral or bilateral) | Resting MBFV (before nitric oxide infusion) | No difference. | 8 |
| Haring and Aichner 46 | Total = 60MA = 17 (MD) MO = 23 (MD) Controls = 20 (14 F/6M) | Bilateral ACABilateral MCABilateral PCA | Resting MBFV | No difference. | 8 |
| Thie et al.66 | Total = 23MX = 11 (MD) Controls = 12 (MD) | Unilateral MCA (left) Unilateral PCA (left) | Neurovascular coupling (cognitive and photic stimulation) | MX had higher CVR to photic stimulation, observation of complex images and cognitive tasks compared to controls. | N/A |
| Totaro et al.45 | Total = 132MA = 44 (39 F/5M) Controls = 88 (MD) | BABilateral ACABilateral MCA Bilateral PCA | Resting MBFV, PI | Migraineurs had higher PI in the MCA compared to controls. | 7 |
| Harer et al.54 | Total = 82IMX = 32 (MD) CMX = 18 (MD) Controls = 32 (MD) | MCA (ipsilateral and contralateral to migraine) | CVR to inhalation of 5%CO2 | MX had higher CRI compared to controls. | N/A |
| Zwetsloot et al.63 | Total = 65MO = 48 (MD) Controls = 17 (10 F/7M) | BAUnilateral MCA | CVR to hyperventilation (1-min hyperventilation) | No difference. | 7 |
| Thomas et al.59 | Total = 20MX = 10 (7 F/3M) Controls =10 (3 F/7M) | Bilateral MCA | CVR to inhalation of 5%CO2 (3–6 min inhalation) and hyperventilation (3-min hyperventilation) | MX had higher CVR to inhalation of 5%CO2 compared to controls. | N/A |
| fMRI Studies | |||||
| Hu et al.73 | Total = 48CM = 24 (15 F/9M) Controls = 24 (15 F/9M) | Angular gyrus Parietal gyrus (inferior, superior) Marginal gyrus (superior) Occipital gyrus (superior) | Neurovascular coupling (cognitive stimuli) | CM had lower CVR in the left inferior parietal gyrus, superior marginal gyrus and angular gyrus but a higher CVR in the right superior occipital gyrus and superior parietal gyrus. | N/A |
| Chen et al.78 | Total = 30EM = 15 (11 F/4M) Controls = 15 (11 F/4M) | Grey matterSuperior temporal gyrus (left hemisphere) | Resting CBF | EM had higher CBF in the left superior temporal gyrus compared to controls. | N/A |
| Hodkinson et al.72 | Total = 34MO = 17 (12 F/5M) Controls = 17 (MD) | Primary somatosensory cortex | Resting CBF | MO had higher regional CBF compared to controls. | N/A |
| Loehrer et al.74 | Total = 2489MX = 456 (365 F/91M)Controls =2033 (100 F/1933M) | BABilateral ICA | Resting CBF | MX had higher CBF in the BA and a higher parenchymal CBF compared to controls. | N/A |
| Zhang et al.75 | Total = 170 MA = 56 (45 F) MO = 60 (48 F) Controls = 54 (39 F) | GlobalGrey matter White matter | Resting CBF | No difference. | N/A |
| Datta et al.71 | Total = 75MA = 25 (21 F/4M) MO = 25 (21 F/4M) Controls = 25 (21 F/4M) | Primary visual cortex | Resting CBF | No difference. | N/A |
| Arkink et al.76 | Total = 45MA = 12 (12 F/0M) MO = 17 (17 F/0M) Controls = 16 (16 F/0M) | Frontal gyrus Temporal gyrus Postcentral gyrus | Resting CBF | MA had higher CBF in the frontal gyrus (medial) but lower CBF in the temporal gyrus (inferior) and postcentral gyrus. MO had higher CBF in the temporal gyrus (inferior, middle) and lower CBF in the frontal gyrus (inferior). | N/A |
| Ances et al.77 | Total = 10MM = 5 (5F/0M)Controls = 5 (5F/0M) | Occipital lobe | Neurovascular coupling (photic stimulation)Resting CBF | MM had a greater increase in cerebral perfusion in response to photic stimulation compared to controls during the mid-follicular phaseNo difference. | N/A |
| NIRS Studies | |||||
| Schytz et al.81 | Total = 24MO = 12 (12 F/0M) Controls = 12 (12 F/0M) | Frontal cortex | Neurovascular coupling (cognitive stimuli): Stroop task | No difference. | N/A |
| Akin et al.80 | Total = 12MX = 6 (5 F/1M) Controls = 6 (4 F/2M) | Frontal cortex | CVR to BHT (20s to 30 s breath hold) | MX had lower ID and R amplitudes of Hb, tHb and oxygen concentrations; therefore lower CVR. | N/A |
| Vernieri et al.48 | Total = 37MA = 16 (13 F/3M) Controls = 21 (16 F/5M) | Bilateral MCAFrontotemporal region | CVR to inhalation of 7%CO2 (90s inhalation) | MA had higher CVR compared to controls. | 5 |
| Resting MBFV | No difference. | ||||
| SPECT Studies | |||||
| Cheng et al.85 | Total = 34MX = 19 (13 F/6M) Controls = 15 (9 F/6M) | Frontal lobe Occipital lobe Parietal lobeTemporal lobe | Resting CBF | MX had lower parenchymal CBF in the frontal, temporal, left parietal and right occipital lobes. | N/A |
| Meyer et al.82 | Total = 64MX = 37 (25 F/12M) Controls = 27 (11 F/16M) | Global Grey matter (cortical, subcortical) White matter | Resting CBF | No difference. | N/A |
| CVR to oral acetazolamide | MX had higher CVR compared to controls. | ||||
| Mirza et al.86 | Total = 61MX = 44 (42 F/2M) Controls = 17 (15 F/2M) | Frontal lobe (inferior, superior) Occipital lobe Parietal lobeTemporal lobe | Resting CBF | MX had lower CBF in the superior frontal and occipital lobes. | N/A |
| Facco et al.83 | Total = 151MA = 20 (15 F/5M) MO = 50 (41 F/9M) TTH = 21 (17 F/4M)Controls = 60 (35 F/25M) | Homologous regions of both the left and right cerebral hemispheres | Resting CBF | MA had lower posterior CBF and lower mean CBF compared to controls. MO had higher mean CBF compared to controls. | N/A |
| Levine et al.84 | Total = 47MA = 15 (MD) MO = 12 (MD) Controls = 20 (MD) | Homologous regions of both the left and right cerebral hemispheres (10 anterior probes, 6 posterior probes). | Resting CBF | MA and MO had lower posterior CBF compared to controls and lower mean CBF compared to controls. | N/A |
| Benedittis49 | Total = 62MA = 35 (27 F/8M) MO = 13 (7 F/6M) Controls = 14 (8 F/6M) | Bilateral ICABilateral MCABilateral VA Frontal lobeOccipital lobeParietal lobeTemporal lobe | Resting CBF, MBFV | No difference. | N/A |
ACA: anterior cerebral artery; BA: basilar artery; BHT: breath hold task; CBFV: cerebral blood flow velocity; CRI: cerebral reactivity index; CVR: cerebrovascular responsiveness; ICA: internal carotid artery; LSM: left-sided migraineurs; MA: migraineurs with aura; MBFV; mean blood flow velocity; MCA: middle cerebral artery; MD: missing data; MM: menstrual migraineurs; MO: migraineurs without aura; MX: mix of migraineurs with and without aura; NOS: Newcastle-Ottawa scale; PCA: posterior cerebral artery; PI: pulsatility index;: RI: resistive index; RSM: right-sided migraineurs; TCD: transcranial Doppler; TTH: tension type headache; VA: vertebral artery; VEFR: visually evoked cerebral blood flow response.